Voltage-dependent Ca2+ channels in resistance arteries from spontaneously hypertensive rats.

Abstract

Alterations in voltage-dependent Ca2+ channels in the arterial smooth muscle cells of spontaneously hypertensive rats (SHR) were investigated using the whole-cell voltage clamp and compared with Wistar-Kyoto (WKY) rats. Single cells were freshly isolated from resistance mesenteric arteries from 4- to 5-week-old (young) and 16- to 18-week-old (adult) SHR. Elevated blood pressure was only evident in adult SHR, not in young SHR. In young rats, the Ca2+ channel current density (current amplitude normalized by cell capacitance) was significantly higher (P < .01) in SHR than in WKY rats at the command potential of -10 mV or higher (with 50 mmol/L Ba2+): The current density at 20 mV was -16.8 +/- 1.1 pA/pF in SHR (n = 38 cells) and -11.0 +/- 0.8 pA/pF in WKY rats (n = 30 cells). In adult rats, the difference in current densities disappeared: -15.9 +/- 1.3 pA/pF in SHR (n = 25 cells) and -15.6 +/- 1.5 pA/pF in WKY rats (n = 29 cells). The ratio of maximal amplitude of T-type current to that of L-type current was low in young SHR (0.10 +/- 0.01) compared with the other three groups (0.16 to 0.20). Neither the activation curve nor the steady-state inactivation curve of SHR was different from that of age-matched WKY rats. However, the activation curves in adult rats were shifted to a hyperpolarized direction compared with those of young rats in both strains. These results suggest that the increased activity of voltage-dependent L-type Ca2+ channels of resistance arteries in young SHR may be related to the development of hypertension. The changes observed in adult rats may be due to a secondary modification of the channel during maturation and the presence of hypertension.